Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a painful neuropathy: Ultrastructural morphometric analysis of axonal alterations
Fixed-diameter polyethylene cuffs applied to the rat sciatic nerve induce a painful neuropathy: Ultrastructural morphometric analysis of axonal alterations
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DOI：
10.1016/0304-3959(95)00077-1
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发表时间：
1996-01-01
期刊：
影响因子：
7.4
通讯作者：
Kruger, L
中科院分区：
文献类型：
--
作者：
Mosconi, T;Kruger, L
将不同内径的聚乙烯套囊应用于大鼠坐骨神经或腓肠神经，目的是诱导标准化神经损伤，通过与神经性疼痛的行为表现相关的纤维尺寸谱变化的形态测量分析来评估。轴突变性和再生的时间顺序与术后 6 周 (PO) 期间疼痛发生和恢复的行为分析同时进行。内径为 0.028-0.030 英寸的袖带松散地封闭幼年大鼠的坐骨神经，并引起相对均匀的轴突变性和“疼痛”。大的有髓鞘轴突经历了早期和持续的数量耗尽。薄髓鞘和无髓鞘轴突群体最初都减少，但后来上升到显着高于对照值的水平，可能是由于：（1）脱髓鞘，（2）髓鞘再生的早期阶段，（3）再生出芽，和/或（4）未受损的无髓鞘轴突的侧支出芽。受损神经的病理改变包括水肿性肿胀、神经束膜肥大、成纤维细胞和胶原蛋白浸润到神经内室、轴突间隙增大以及轴突堆积的顺序和密度降低。动物在术后第 2 周表现出最大程度的疼痛相关行为，包括步态和姿势不对称以及对机械压迫和寒冷的过敏，并在术后 4 周时基本恢复。在广泛的纤维频谱改变范围内实现了一致的疼痛行为表现；然而，在本研究中使用最大的袖带或“手镯”时，产生了显着的轴突纤维谱变化，但没有引起疼痛相关行为，这表明有髓轴突数量的减少并不总是足以引起疼痛。 0.010'' ID 袖带和 14 天 PO 存活后，腓肠神经病变获得了类似的形态测量和病理结果。考虑到轴突改变和疼痛之间缺乏相关性，损伤部位理想神经内微环境的改变可能是外周疼痛机制的关键组成部分；这些包括生化环境的变化、神经内压力的增加以及相对完整的无髓鞘轴突群体中伤害感受器敏感性或冲动传播的改变。
Polyethylene cuffs of varying inner diameters were applied to the rat sciatic or sural nerve with the aim of inducing a standardized nerve injury, as assessed by morphometric analyses of fiber-size spectrum alterations, associated with behavioral manifestations of neuropathic pain. The temporal sequence of axonal degeneration and regeneration was examined in parallel with behavioral analyses of pain initiation and recovery over a 6-week postoperative (PO) period. Cuffs of 0.028-0.030'' inner diameter loosely enclosed sciatic nerves of young rats and elicited relatively uniform axonal degeneration and 'pain'. Large myelinated axons underwent an early and sustained numerical depletion. Both the thinly myelinated and unmyelinated axon populations were initially diminished, but later rose to levels significantly greater than control values, likely the result of: (1) demyelination, (2) early stages of remyelination, (3) regenerative sprouting, and/or (4) collateral sprouting of undamaged unmyelinated axons. Pathological alterations of the injured nerve included edematous swelling, hypertrophy of the perineurial sheath, infiltration of fibroblasts and collagen into the intraneurial compartment, increasing interaxonal space and decreasing order and density of axonal packing. Animals displayed maximal pain-related behaviors, including gait and postural asymmetries and hypersensitivity to mechanical compression and cold, during the 2nd week PO and had largely recovered by similar to 4 weeks PO. Consistent behavioral manifestations of pain were achieved over a wide range of fiber spectrum alteration; however, with the largest cuffs or 'bracelets' used in this study, a substantial axonal fiber spectrum change was produced without inducing pain-related behavior, suggesting that decrement in the number of myelinated axons was not always sufficient to elicit pain. Similar morphometric and pathological results were achieved with sural neuropathy after 0.010'' ID cuffs and 14 days PO survival. Considering the lack of correlation between axonal alterations and pain, modification in the Ideal intraneurial microenvironment at the site of injury may be a key component of peripheral pain mechanisms; these include changes in the biochemical milieu, increased intraneurial pressure, and altered nociceptor sensitivity or impulse propagation in the relatively intact unmyelinated axon population.